Biomarkers in Pediatric ARDS: Future Directions

Orwoll, Benjamin E.; Sapru, Anil

Additional types of non-protein biomarkers that may have utility in pediatric lung disease include several types of extracellular complexes, including circulating MPs (also known as microvesicles or cellular exosomes) and neutrophil extracellular traps (NET). MPs are a class of cell-derived vesicles that develop by budding off from the membrane of many different cell types and range in size from 50 nm to 1 μm. They may carry a variety of different contents, including proteins, lipids, and nucleic acids, and have a wide variety of potential effects in lung injury depending on their origin, location, and contents (181) . MPs have been isolated from the blood (182) and BAL fluid (183) in adult ARDS patients and have been subtyped based on their cellular origin with certain subtypes, such as leukocyte-derived MPs, demonstrating possible prognostic significance. MP-based biomarkers may prove useful in future studies of children with ARDS and may also have potential as therapeutic agents able to ferry payloads of drugs or other substances to specific target tissues based molecular tropism (184) . NETs are derived from programed death of circulating neutrophils and are composed of extruded cellular contents, including nuclear chromatin, histone proteins, and other various proteins. These NETs have antimicrobial activity and have been proposed as a host defense mechanism (185) . NETs have been detected in the plasma and BAL of patients with transfusion-related acute lung injury (TRALI) (186) and critical illnesses (187) , and circulating extracellular histones, the major protein component of NETs, are directly cytotoxic and elevated in the setting of trauma-associated lung injury (188) . NETs, MPs, and other extracellular complexes represent potentially useful biomarkers in children with ARDS.